Burroughs A K, Sprengers D, McCormick P A
Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
Aliment Pharmacol Ther. 1987 Feb;1(1):3-21. doi: 10.1111/j.1365-2036.1987.tb00601.x.
beta-Adrenoceptor blockers always change splanchnic haemodynamics in cirrhotic patients. Azygous blood flow, as a measure of collateral circulation including that through varices, is always reduced, but the effects on portal pressure, whether measured directly or by the wedged hepatic venous pressure, are variable. The initial correlations between a 25% reduction of resting pulse rate and similar percentage reduction in the wedge-free hepatic venous gradient, has not been reproduced in subsequent studies. Therefore, to study the effect of changes in haemodynamic indices and the likelihood of variceal bleeding, direct measurements of such indices need to be made in clinical trials. At present there are no haemodynamic or clinical factors which can be used to select patients who will have a good therapeutic response to propranolol other than those documented in the first clinical trial of propranolol for the prevention of variceal re-bleeding from Paris. Thus the hypothesis that beta-adrenoceptor blockers may lessen the incidence of bleeding in cirrhotics, by partially reducing portal pressure or flow or both, needs testing in further clinical studies. The selection criteria of the first clinical trial of propranolol in Paris need to be confirmed. Two subsequent trials, in which patients were not selected but in which many patients had similar clinical characteristics to the Paris patients, could not confirm a therapeutic effect of propranolol. No fatal complications due to propranolol administration have been reported in cirrhotic patients. Complications are reversible. Pharmacological treatment including beta-adrenoceptor blockade appears ideal for trials of primary prevention of variceal bleeding. Some preliminary results including use in decompensated cirrhotics are encouraging. However, as for trials for prevention of re-bleeding, the design and analysis of such trials needs careful evaluation to take into account the outcome of patients who discontinue medication, whether due to simple noncompliance or due to side-effects, and also the influence of abstinence from alcohol on bleeding from varices.
β-肾上腺素能受体阻滞剂总会改变肝硬化患者的内脏血流动力学。奇静脉血流量作为侧支循环（包括通过静脉曲张的侧支循环）的一项指标，总是会降低，但对门静脉压力的影响，无论是直接测量还是通过肝静脉楔压测量，都是可变的。静息心率降低25%与无肝静脉楔压梯度降低相似百分比之间的最初相关性，在后续研究中并未重现。因此，为了研究血流动力学指标变化的影响以及静脉曲张出血的可能性，需要在临床试验中对这些指标进行直接测量。目前，除了普萘洛尔预防静脉曲张再出血的第一项巴黎临床试验中记录的那些因素外，没有任何血流动力学或临床因素可用于选择对普萘洛尔有良好治疗反应的患者。因此，β-肾上腺素能受体阻滞剂可能通过部分降低门静脉压力或血流量或两者兼而有之来降低肝硬化患者出血发生率这一假设，需要在进一步的临床研究中进行验证。普萘洛尔在巴黎的第一项临床试验的选择标准需要得到确认。随后的两项试验没有对患者进行选择，但许多患者具有与巴黎患者相似的临床特征，这两项试验未能证实普萘洛尔的治疗效果。在肝硬化患者中，尚未有因使用普萘洛尔而导致致命并发症的报道。并发症是可逆的。包括β-肾上腺素能受体阻滞剂在内的药物治疗似乎是静脉曲张出血一级预防试验的理想选择。一些初步结果，包括用于失代偿期肝硬化患者的结果令人鼓舞。然而，对于预防再出血的试验，此类试验的设计和分析需要仔细评估，以考虑因单纯不依从或副作用而停药的患者的结局，以及戒酒对静脉曲张出血的影响。
